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A model describing the behaviour of charge carriers in semiconducting polymers both in the hopping-like and metal-like regimes is developed, and used to quantify charge carrier localization and other transport parameters in organic semiconductors.

cellSTAAR advances noncoding rare variant association analysis by integrating single-cell genomics data.

The noisy dynamics of biological neurons is vital for cognition, but artificial neurons failed to replicate it. Here, the authors show that neurons built with diffusive memristors can emulate the balance of stochastic and deterministic activity in biological neurons, while surpassing them in computational efficiency.

Padawer-Curry et al. show that the hallucinogenic 5-HT2A receptor agonist DOI alters neurovascular coupling in mice, with implications for the interpretation of human fMRI studies of psychedelics.

Using data from a single time point, passenger-approximated clonal expansion rate (PACER) estimates the fitness of common driver mutations that lead to clonal haematopoiesis and identifies TCL1A activation as a mediator of clonal expansion.

MultiSTAAR provides a general and flexible statistical framework for functionally informed multi-trait rare variant analysis of biobank-scale sequencing studies by jointly analyzing multiple traits and incorporating annotation information.

Pre-malignant cells harbouring oncogenic mutations can populate and spread throughout a tissue. Here, using a rainbow mouse system, the authors explore how clonal expansion in the mouse intestine might explain high levels of intra-tumoural heterogeneity observed in the disease.

Analyses of genome and exome sequencing data identify rare coding and structural variants associated with atrial fibrillation and highlight genetic links between atrial fibrillation and cardiomyopathies.

Modulating mitochondrial NAD⁺ levels by changing the expression of the mitochondrial NAD⁺ transporter, SLC25A51, Mukherjee et al. demonstrate that mitochondrial, rather than cytosolic or nuclear, NAD⁺ levels are a key determinant of the rate of liver regeneration.

Head motion is an artifact in structural and functional MRI signals, and some traits or groups are more strongly correlated with motion than others. Here the authors describe a method to attribute a motion impact score to specific trait-functional connectivity relationships.

The authors find the human red nucleus is functionally connected with action and motivated behavior networks, instead of motor-effector networks. They argue the red nucleus implements goal-directed behavior, integrating behavioral valence and action plans.

Interstellar aldehydes are essential intermediates to form biomolecules necessary for the origins of life, but their formation mechanisms have remained elusive. Here, the authors elucidate the formation pathways of biologically relevant aldehyde, lactaldehyde, and its isomers in interstellar ice analogs composed of carbon monoxide and ethanol.

Analysis of 97,691 high-coverage human blood DNA-derived whole-genome sequences enabled simultaneous identification of germline and somatic mutations that predispose individuals to clonal expansion of haematopoietic stem cells, indicating that both inherited and acquired mutations are linked to age-related cancers and coronary heart disease.

Although the common genetic variants contributing to blood lipid levels have been studied, the contribution of rare variants is less understood. Here, the authors perform a rare coding and noncoding variant association study of blood lipid levels using whole genome sequencing data.

Nshanian et al. investigate the differential effects of the short-chain fatty acids propionate and butyrate on chromatin remodelling and gain insight into the mechanisms that drive selective histone acylation.

Here the authors conduct a multi-ancestry meta-analysis of telomere length, used diverse approaches to identify genes underlying association signals, and experimentally validated POP5 and KBTBD6 as regulators of telomere length in human cells.

A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.

STAARpipeline is a comprehensive framework for flexible and scalable rare-variant association analysis using whole-genome sequencing data and annotation information.

Healthy adults were tracked before, during and after high doses of psilocybin and methylphenidate to assess how psychedelics can change human brain networks, and psilocybin was found to massively disrupt functional connectivity in cortex and subcortex with some changes persisting for weeks.

Platelet aggregation is associated with myocardial infarction and stroke. Here, the authors have conducted a whole genome sequencing association study on platelet aggregation, discovering a locus in RGS18, where enhancer assays suggest an effect on activity of haematopoeitic lineage transcription factors.

Temporal multi-omic analysis of tissues from rats undergoing up to eight weeks of endurance exercise training reveals widespread shared, tissue-specific and sex-specific changes, including immune, metabolic, stress response and mitochondrial pathways.

A study demonstrates a public generator of random numbers based on device-independent techniques, with the randomness being fully auditable and traceable.

The goal of the 1000 Genomes Project is to provide in-depth information on variation in human genome sequences. In the pilot phase reported here, different strategies for genome-wide sequencing, using high-throughput sequencing platforms, were developed and compared. The resulting data set includes more than 95% of the currently accessible variants found in any individual, and can be used to inform association and functional studies.

Pooling participant-level genetic data into a single analysis can result in variance stratification, reducing statistical performance. Here, the authors develop variant-specific inflation factors to assess variance stratification and apply this to pooled individual-level data from whole genome sequencing.

The autoinflammatory pathology associated with alteration of the ZBD domain of the RNA-editing enzyme ADAR1 is driven by signalling that is dependent on the nucleotide sensor ZBP1.

Studies show the cancer transcriptome correlates poorly with the cancer proteome, questioning the role of chromatin regulation. Here the authors demonstrate proximal-gene-body chromatin elements and transcription predict abundances of differentially expressed proteins in thyroid and breast cancers.

This overview of the ENCODE project outlines the data accumulated so far, revealing that 80% of the human genome now has at least one biochemical function assigned to it; the newly identified functional elements should aid the interpretation of results of genome-wide association studies, as many correspond to sites of association with human disease.

Analysis of whole-genome sequences of 25,465 individuals of European ancestry shows that rare variants contribute substantially to the heritability of height and body mass index.

The goals, resources and design of the NHLBI Trans-Omics for Precision Medicine (TOPMed) programme are described, and analyses of rare variants detected in the first 53,831 samples provide insights into mutational processes and recent human evolutionary history.

Most studies of the genetics of the metabolome have been done in individuals of European descent. Here, the authors integrate genomics and metabolomics in Black individuals, highlighting the value of whole genome sequencing in diverse populations and linking circulating metabolites to human disease.

An integrated transcriptome, genome, methylome and proteome analysis of over 200 lung adenocarcinomas reveals high rates of somatic mutations, 18 statistically significantly mutated genes including RIT1 and MGA, splicing changes, and alterations in MAPK and PI(3)K pathway activity.

Integrating independent large-scale pharmacogenomic screens can enable unprecedented characterization of genetic vulnerabilities in cancers. Here, the authors show that the two largest independent CRISPR-Cas9 gene-dependency screens are concordant, paving the way for joint analysis of the data sets.

Many viral diagnostic approaches require nucleic acid extraction and amplification prior to detection. Here, the authors develop a method based on type III CRISPR systems which allows sequence specific capture, concentration, and detection of viral RNA directly from patient samples.

Arany and colleagues integrate metabolomics data, tissue RNA-sequencing data and proteomics data from explanted hearts of patients with end-stage heart failure to provide a comprehensive ‘multi-omic’ evaluation of the metabolic pathways affected by heart failure.

The stability of polymer electrolyte membrane fuel cells is limited by the degradation of the cathode catalyst during repetitive start-up/shut-down events — a parasitic oxygen reduction reaction on the anode causes an instantaneous potential jump at the cathode. The issue is now addressed by selectively suppressing the oxygen reduction reaction on the anode by exploiting the metal–insulator transition behaviour of Pt/H_xWO₃ catalysts.

Tagging and tracking the blood plasma proteome as a discovery tool reveals widespread endogenous transport of proteins into the healthy brain and the pharmacologically modifiable mechanisms by which the brain endothelium regulates this process with age.

The methylation status of circulating cell-free DNA (cfDNA) can be informative about recent cell death events. Here the authors present an approach to determine the tissue origins of cfDNA, using a reference methylation atlas of 25 human tissues and cell types, and find that cfDNA from patients reveals tissue contributions that agree with clinical findings.

Johnson et al. report that loss of leukaemia inhibitory factor receptor (LIFR) signalling reduces the expression of genes associated with dormancy in metastatic breast cancer cells, and promotes bone marrow colonization and osteoclastogenesis.

A genetic mouse model is used to reveal a two-pronged mechanism of fructose-induced de novo lipogenesis in the liver, in which fructose catabolism in hepatocytes provides a signal to promote lipogenesis, whereas fructose metabolism by the gut microbiota provides acetate as a substrate to feed lipogenesis.

The functions of non-coding regulatory elements can be systematically studied genome-wide at high throughput in human cells via their Cas9-mediated deletion through libraries of paired single-guide RNAs targeting both ends of each element.

A genome-wide association study including over 76,000 individuals with schizophrenia and over 243,000 control individuals identifies common variant associations at 287 genomic loci, and further fine-mapping analyses highlight the importance of genes involved in synaptic processes.

GIANT, a genetically informed brain atlas, integrates genetic heritability with neuroanatomy. It shows strong neuroanatomical validity and surpasses traditional atlases in discovery power for brain imaging genomics.

Large-scale, next-generation sequencing collaborations have identified drivers and vulnerabilities of urothelial carcinoma. In this Review, the authors discuss the mutational landscape of urothelial carcinoma, including specific mutations in pathways and driver genes and describe how the next generation of therapies will be based on patient-specific targetable mutations observed in individual tumours.

MetaSTAAR enables functionally informed rare variant association analysis in biobank-scale cohorts using an efficient, sparse matrix approach for summary statistic storage.

It is known that exercise influences many human traits, but not which tissues and genes are most important. This study connects transcriptome data collected across 15 tissues during exercise training in rats as part of the Molecular Transducers of Physical Activity Consortium with human data to identify traits with similar tissue specific gene expression signatures to exercise.

Using a multi-omics approach, the authors examine the molecular drivers of sexual dimorphism in the subcutaneous adipose tissue from sedentary and endurance-trained rats. These data provide a valuable resource for adipose tissue-related research.

The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.

Macrophages alter their metabolism in response to infection. The authors show that resting macrophages generate nicotinamide adenine dinucleotide via de novo synthesis, but activated and aged cells suppress the rate-limiting enzyme quinolinate phosphoribosyltransferase to regulate mitochondrial and immunological functions.